The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress

TLDR

The stress response is a coordinated behavioral and physiological reaction mediated by corticotropin‑releasing factor, which activates the hypothalamic‑pituitary‑adrenal axis and releases glucocorticoids that are regulated by feedback inhibition and diverse afferent inputs from limbic, midbrain, and brain‑stem nuclei. This review aims to discuss the role of the HPA axis in integrating adaptive responses to stress. The authors outline the key neuronal and endocrine systems—such as limbic afferents, brain‑stem noradrenergic neurons, sympathetic and parasympathetic circuits—that regulate HPA activity and maintain homeostasis during aversive stimuli.

Abstract

Animals respond to stress by activating a wide array of behavioral and physiological responses that are collectively referred to as the stress response. Corticotropin-releasing factor (CRF) plays a central role in the stress response by regulating the hypothalamic-pituitary-adrenal (HPA) axis. In response to stress, CRF initiates a cascade of events that culminate in the release of glucocorticoids from the adrenal cortex. As a result of the great number of physiological and behavioral effects exerted by glucocorticoids, several mechanisms have evolved to control HPA axis activation and integrate the stress response. Glucocorticoid feedback inhibition plays a prominent role in regulating the magnitude and duration of glucocorticoid release. In addition to glucocorticoid feedback, the HPA axis is regulated at the level of the hypothalamus by a diverse group of afferent projections from limbic, midbrain, and brain stem nuclei. The stress response is also mediated in part by brain stem noradrenergic neurons, sympathetic andrenomedullary circuits, and parasympathetic systems. In summary, the aim of this review is to discuss the role of the HPA axis in the integration of adaptive responses to stress. We also identify and briefly describe the major neuronal and endocrine systems that contribute to the regulation of the HPA axis and the maintenance of homeostasis in the face of aversive stimuli.